Process for producing certain substituted benzoxazoles



United States Paten 9 r PROCESS FOR PRODUCING CERTAIN SUBSTI- TUTEDBENZOXAZOLES Adolf Emil Siegrist, Base], and Franz Ackermann, Binningen,Switzerland, assignors to Ciba Limited, Basel, Switzerland, a firm ofSwitzerland N Drawing. Application May 13, 1958 Serial No. 734,848

4 Claims. (Cl. 260- 240) This is a continuation in part of ourapplication Ser. No. 591,275, filed June 14, 1956 (abandoned since thefiling of the present application).

This invention provides new oxazole compounds which like, for example,the compound of the formula correspond to the general formula in whichR, and R2 each iepres'ents an aryl radical, R being bound to the 'OHgroup and --NH- group and R being fused on to the oxazole ring in themanner indicated in the formula.

The invention also provides a process for the manufacture of thecompounds of the above Formula 2, wherein two molecular proportions ofan ortho-hydroxyaminoaryl compound are condensed with 1 molecularproportion of thiomalic' acid or a functional derivative thereof.

The ortho-hydroxy-aminoaryl compounds used as starting materials may be,for example, of the naphthalene series or advantageously of the benzeneseries, and there are-advantageously used monocyclicorthohydroxy-aminoaryl compounds of the benzene series. The startingmaterials may contain, in addition to the ortho-hydroxy-amiuoarylgrouping, further sub'stituents, for example, lower alkyl or alkoxygroups, such as ethyl, methyl, ethoxy or methoxy groups, or halogenatoms such as chlorine, or nitro groups. As examples oforthohydroxy-aminoaryl compounds there'may be mentioned:1-amino-2-hydroxynaphthalene, I-amino-2-hydroxybenzene, lamin'o-2-hydroxy-5-methylbenzene, 1-arnino-2=hydroxy-4-methylbenzene,l-amino 2-hydroxy-5=methoxybenzene, 1-amino-2-hydroxy-3 5-dimet-hylbenzene; 1-amino-2-hydroxy 5-tertiary butylbenzene,1-amino-2-hydroxy-4- or -5'-'nitfobenzene,1-amino-2-hydroxy-5-chlorobenzene and 1-arnino-2-hydroxy-3S-dichlorobenzene.

The other starting materials used in the present process are thiomalicacid and functional derivatives thereof, for example, monoesters ordiesters thereof. Among the esters of the aforesaid dicarboxylic acidthere may be used, more especially, those having radicals of alkanols oflow molecular weight, for example, the dimethyl ester or diethyl ester.

The ortho-hydroxy-aminoaryl compounds are condensed with the thiomalicacid or functional derivative thereof in the molecular ratio 2:1. Thestarting materials are therefore brought together for the reactionapproximately in this ratio, and it is preferable to use a small excessof the thiomalic acid or derivative thereof rather than an excess of theaminoaryl compound. In this manner the formation of undesiredby-products and loss of the starting materials are to a very greatextent avoided.

Thev condensation is advantageously carried out at a raised temperature,and preferably in an inert organic solvent. As solvents there are usedprincipally high boiling solvents, for example, substitution products ofbenzene, such as monochloi'obenzene, dichlorobenzenes, trichlorobenzenesor nitrobenzenes, or especially high boiling hydrocarbons of the benzeneseries, such as toluene, xylene or cumene. The reaction temperature isadvantageously within the range of 200 C. It is of advantage to work atthe boil in one of the aforesaid solvents. Hydrogen sulfide is formedand escapes during the reaction, and water likewise formed may beseparated from the distilled solvent with the aid of a water separatorand the solvent returned to the reaction mix ture.

Although the precise mechanism of the reaction is not known, it is quiteclear from analyses of the end products and the formation of water andhydrogen sulfide that 2 molecules of the aminoaryl compound combine with1 molecule of thiomalic acid accompanied by the splitting off of 3molecules of Water and 1 molecule of hydrogen sulfide with formation ofone oxazole ring.

The oxazole compounds of the Formula 2 are valuable intermediateproducts which can be used, forexample, for the manufacture of dyestuffsor optical brighten} ing agents. For example, they can be converted bymeans of agents capable of splitting on water into di-(aryloxazolyl)-ethylenes, which are obtained in this manner much moreeasily and in a purer state than by the known methods of heatinghydroxy-aminoaryl compounds with 'succinic acid, and "thendehydrogenating, or by melting oxy-cor'npoiiiids with ruma'rie abid ofmaleic acid.

The following examples illustrate the invention, the parts andpercentages being by Weight unless otherwise stated, and therelationship of parts by weight to parts by volume beihg the same asthat of the kilogram to the liter:

Example 1 66.5 parts of lamino 2 hydroxy-5-inethylbenzene are stirredwith 700 parts of 'chlorobenzene with the exclusion of air. There arethen added 37.5 parts of dzl-thibmalic acid, the mixture is heated inthe course of about 30 minutes to C., then stirred for 12 hours at 130-132 C. While distilling off and removing the Water formed by thereaction and the hydrogen sulfide. The chlorobenzene is then distilledoff with steam. 'After cooling the reaction mixture, it is filtered andthe filter residue is recrystallized from aqueous alcohol. There isobtained a pale crystalline powder melting at ZOO-201 C., whichcorresponds to the formula Analysis.C H O N calculated: (3:70.11,H=5.23, N=9.09. Found: (3:69.95, H=5.39, N=8.99.

which melts at 183-184 C. after recrystallization from a mixture ofmethylene chloride and methanol.

By using, instead of 66.5 parts of l-amino-Z-hydroxy- S-methylbenzene, amolecularly equivalent quantity of 1- amino2-hydroxybenzene there isobtained the compound of the formula which melts at 189190 C. after.recrystallization from a mixture of alcohol and water.

Analysis.-C H O N calculated: C=68.56, H==4.32, N=10.00. Found: C=68.91,H=4.52, N=9.89.

By melting the latter compound with zinc chloride there is obtaineda:fi-di[benzoXazoy1-(2)J-ethylene of the formula melting at 242-243 C.after recrystallization from dioxane.

Example 2 is obtained melting at 192-194 C. Analysis.C H O N- Clcalculated: C=55.03, H: 2.89, N=8.02, Cl=20.31. Found: C=54.96, H=3.03,N=8.1l, Cl=20.06.

By melting the latter product with zinc chloride there is obtaineda:fl-di-[5-chlorobenzoxazolyl-(2) l-ethylene of the formula 0 0 CCH=CHC01 N 5 which melts at 262-263 C. after recrystallization from 6 dioxane.

4 Example 3 If the procedure of Example 1 is followed and instead of1-amino-2-hydroxy-S-methylbenzene there is used 1-amino-Z-hydroxy-4-methylbenzene as starting material the compound of theformula is obtained. By melting the latter with zinc chloride at -180 C.for several hours there is obtained aIB-di-[fi-methyl-benzoxazolyl-(2)1ethylene of the formula which afterrecrystallization from a mixture of methylene chloride and methanol,melts at -191 C.

What is claimed is:

1. Process for the manufacture of an oxazole compound, which comprisescondensing in an organic solvent at a temperature between 100 and 200 C.two molecular proportions of a compound of the formula in which Zrepresents a member selected from the group consisting of a hydrogenatom, a methyl group and a chlorine atom, with one molecular proportionof thiomalic acid.

2. Process for the manufacture of an oxazole compound which comprisescondensing in an organic solvent at a temperature between 100 and 200 C.two molecular proportions of 1-amino-2-hydroxybenzene with one molecularproportion of thiomalic acid.

3. Process for the manufacture of an oxazole compound which comprisescondensing in an organic solvent at a temperature between 100 and 200 C.two molecular proportions of 1-amino-2-hydroxy-S-methylbenzene with onemolecular proportion of thiomalic acid.

4. Process for the manufacture of an oxazole compound which comprisescondensing in an organic solvent at a temperature between 100 and 200 C.two molecular proportions of 1-amino-2-hydroxy-5-chlorobenzene with onemolecular proportion of thiomalic acid.

References Cited in the file of this patent UNITED STATES PATENTS2,323,503 Wilson July 6, 1943 2,483,392 Meyer et al Oct. 4,-19492,488,094 Graenacher et al. Nov. 15, 1 949 2,807,622 Holbro et al Sept.24, 1957 2,828,317 Siegrist et a1 Mar. 25, 1958 OTHER REFERENCESMedinger: .I. Prakt. Chemie 2 vol 86, pp. 345-339 Q1913.)-

2. PROCESS FOR THE MANUFACTURE OF AN OXAZOLE COMPOUND WHICH COMPRISESCONDENSING IN AN ORGANIC SOLVENT AT A TEMPERATURE BETWEEN 100 AND 200*C.TWL MOLECULAR PROPORTIONS OF 1-AMINO-2-HYDROXYBENZENE WITH ONE MOLECULARPROPORTION OF THIOMALIC ACID.